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Major depressive disorder is a serious public mental health concern with prevalent sex differences, affecting twice as many women as men. The non-competitive NMDA receptor antagonist ketamine is being used clinically at low doses as an antidepressant for treatment-resistant patients, yielding rapid and robust therapeutic effects lasting up to one week. However, it is likely that long-term maintenance of ketamine's antidepressant effects will require repeated administration in many patients. We have recently shown that female rats have a heightened sensitivity to ketamine's antidepressant effects that is mediated by gonadal hormones. Importantly, ketamine is also recreationally abused and is a Schedule III drug in the U.S. Determining the consequences and sex differences therein of repeated sub-anesthetic ketamine dosing is vital to the viability of the drug as a clinical antidepressant with regard to its pharmacologically rewarding and addictive properties. In this study, using the conditioned place preference, we assessed rewarding properties of several doses of ketamine (0, 2.5, 5.0, or 10 mg/kg i.p.) in adult male and female Sprague-Dawley rats. Additionally, animals' locomotor activity was monitored upon the first and sixth ketamine injections to assess behavioral sensitization to the locomotor activating effects of the drug. Our results show that male rats developed a place preference for only the 10 mg/kg ketamine dose. In contrast, females did not develop a place preference to any dose of ketamine. Both males and females displayed a significant increase in locomotor activity between the first and sixth administration of 5.0 and 10 mg/kg ketamine, which suggests that they developed a behavioral sensitization to these doses. These findings suggest that repeated treatment with ketamine induces dose- and sex-dependent effects on reward state and behavioral sensitization in male and female rats.